The goal of this research program is to exploit ruthenium coordination chemistry in the design and development of clinically useful ruthenium-97 radiopharmaceuticals with a biochemical basis for tissue localization. Biodistribution, pharmacokinetic, and metabolic studies will be carried out to evaluate the potential of a promising new pancreatic imaging agent based on a pentaammineruthenium(III) complex of beta-(4-pyridyl)-alpha-alanine. To understand how the molecular properties of organoruthenium complexes can be manipulated to aid in the rational design of new radiodiagnostic agents, a series of pyridylalanine ruthenium complexes in which counterion, ionic charge, auxiliary ligands, and stereochemistry are systematically varied will be synthesized. The resulting complexes will be characterized by electronic spectroscopy (UV/VIS/IR), nuclear magnetic resonance, and elemental analysis. In vivo structure-activity relationships will be established for the ruthenium-103 labeled complexes to allow selection of a particular coordination environment most advantageous for general application in achieving tissue specificity in the design of ruthenium-97 radiopharmaceuticals through labeling small, biologically active molecules. To develop a versatile ruthenium reagent for radiolabeling proteins, complexes capable of binding to serum proteins by reaction of a coordinated ligand or via bonding to the metal center will be synthesized and evaluated in vitro and in vivo to ascertain how the physical properties, biodistribution, stability, biologic half-life, blood clearance, and antigenic properties compare with those of the radioiodine labeled protein. To develop scintigraphic agents based on arene ruthenium chemistry, several simple analogues will be synthesized for comparative biodistribution studies to evaluate whether or not modification of the organic ligands in these complexes can be employed to predictably target ruthenium-97 in vivo.